NsCuCy NPs Are Used For Type-Ⅰ Photodynamic Therapy Of Breast Tumor

Cancer remains one of the most serious diseases affecting human health.Photodynamic therapy（PDT）,as a new treatment mode,has the advantages of non-invasive,high selectivity and less side effects compared with traditional treatment,and has a broad application prospect in cancer treatment.However,the traditional type II PDT dependent on singlet oxygen（¹O₂）has poor therapeutic effect on hypoxic tumors due to the oxygen-dependent mode.On the other hand,studies have shown that type I PDT is superior to type II PDT in tumor therapy due to reduced oxygen dependence.Moreover,hydroxyl radicals（·OH）produced by the type I PDT process are considered to be the most aggressive reactive oxygen species（ROS）,which can directly react with a variety of important biomacromolecules.Therapeutic strategies based on·OH generation have been used as a promising therapeutic approach for improving anti-cancer efficiency.In this work,composite nanoparticles（NSCuCy）were constructed by means of aggregation-induced luminescence（AIE）active type-Ⅰphotosensitizers NS-STPA and Cupric cysteamine nanoparticles（Cu Cy NPs）to promote the formation of typeⅠPDT and·OH.Preparation and characterization of NSCuCy NPs.DSPE-PEG₂₀₀₀,NS-STPA and NH₂-PEG-FA were introduced into the catalyst Cu Cy NPs aqueous solution dispersion,and the nanocomposite NSCuCy was assembled by nano-coprecipitate method.The particle size of NSCuCy NPs was about 133 nm by particle size potential analysis and high resolution transmission electron microscopy（TEM）,which showed good morphology,structure and dispersion.In acidic tumor microenvironment（TME）,the·OH yield of NSCuCy NPs was 1.5times higher than that of NS-STPA NPs,showing better hypoxia tolerance and glutathione（GSH）resistance.And the excellent photothermal effect of NSCuCy NPs accelerates the Fenton reaction and promotes the transformation from·O₂^-to·OH.It is expected that NSCuCy NPs has better PDT performance and antitumor activity.Antitumor evaluation of NSCuCy NPs.Flow cytometry and laser confocal microscopy verified that NSCuCy NPs could be internalized into human breast cancer cells（MCF-7）and distributed in the cytoplasm,with the ability of intracellular imaging,and MTT assay results showed that the anti-tumor evaluation of NSCuCy NPs reached about 85%of tumor cell mortality.In addition,tumor cell apoptosis and cell death staining showed excellent killing effect.After injection through mouse tail vein,NSCuCy NPs concentrated in the tumor site.After 660 nm laser irradiation,the tumor volume and weight of NSCuCy NPs+L group were significantly lower than those of other treatment groups.In addition,tumor H&E and TUNEL staining results showed a large number of apoptosis and necrosis in the NSCuCy NPs+L group.There was no significant change in body weight and no significant damage in H&E staining of major tissues and organs during treatment,which proved that NSCuCy NPs had good biological safety.This therapeutic nano platform has verified that Cu Cy promotes type I PDT process by catalyzing Fenton reaction,which can significantly improve·OH yield,and has clinical application and transformation potential.